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阿克特和AMPK激活剂在患有双相情感障碍的患者的神经元中挽救过度兴奋性
Anouar Khayachi1, Malak Abuzgaya1, Yumin Liu1
1Montreal Neurological Institute, Department of Neurology & Neurosurgery, McGill University, Montréal, Quebec, Canada.
EBioMedicine
|May 21, 2024
概括
通过改变神经元活动,在一些患者中有效治疗双相情感障碍 (BD). 新的策略可能涉及Akt激活剂对响应的病例和AMPK激活剂对不响应的病例.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 细胞生物学 细胞生物学
背景情况:
- 双极性障碍 (BD) 影响全球大约1%的成年人.
- (Li) 是BD的主要情绪稳定剂,但其有效性仅限于一小部分患者,其机制尚不清楚.
- 了解李的作用对于开发有针对性的疗法至关重要.
研究的目的:
- 研究BD中神经元过活性的潜在机制.
- 阐明在响应性和非响应性患者衍生的神经元中的作用模式.
- 确定BD治疗的新型治疗点.
主要方法:
- 利用来自BD患者的诱导多能干细胞 (iPSC) 衍生神经元,分类为对有反应 (LR) 或对无反应 (LNR).
- 采用多奥米克方法,包括电生理学,成像,生物化学,转录组学和蛋白组学.
- 分析了基因表达,细胞信号和离子运输的变化.
主要成果:
- 选择性地拯救了LR神经元中的神经元过活,与Na+导电率的变化有关.
- 转录组分析揭示了BD神经元中的改变途径,包括谷氨酸的传输,细胞信号和离子运输.
- 确定了改变的Akt信号作为LR神经元中的潜在效应,Akt激活模仿的效应.
- 观察到AMP激活蛋白激酶 (AMPK) 激活在LR和LNR神经元中逆转了神经网络活动的增加.
结论:
- 阿克特激活剂代表了对响应性BD患者的潜在治疗策略.
- AMPK激活剂可能为不响应 (LNR) 的BD患者提供治疗方法.
- 这些发现为双相情感障碍的个性化治疗策略铺平了道路.
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